A novel DRAK inhibitor, SC82510, promotes axon branching of adult sensory neurons in vitro

Recently, a new potent protein kinase inhibitor, SC82510, was identified acting on DRAK2 and stimulating axon outgrowth at low concentrations. DRAK is the Drosophila homologue of death-associated protein kinase that phosphorylates myosin-II regulatory light chain in a similar fashion as ROCK, the downstream target of RhoA mediating axon outgrowth inhibition. While higher concentrations of this novel compound exhibited toxic effects, significant promotion of process outgrowth of PC12 cells and of adult primary neurons was observed at 1 nM which could be further enhanced by addition of a neuronal growth factor (FGF-2). Unlike the effects of ROCK inhibitors on axon outgrowth that stimulate both, elongation and branching, SC82510 primarily promoted axon branching, whereas axon elongation was not increased in this cell culture model of peripheral axon regeneration.